Abstract Details

Title Association Study of Late-Onset Alzheimer's Disease Risk Variants and Risk for Posterior Cortical Atrophy

Topic Aging and Dementia

Presentation(s) (-)

Poster/Presentation
Number 003

Objective

Background Recent GWAS of LOAD case-control series identified single nucleotide polymorphisms (SNPs) at nine loci which associate with disease risk. Investigation of these variants for their influence on atypical variants of AD may provide valuable information regarding the phenotypic spectrum of AD that may be vulnerable to these genetic risk factors. Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by predominant visuospatial impairment, relative sparing of memory and focal or asymmetric involvement of the parieto-occipital cortices. The most common underlying pathology in PCA is AD neuropathology in these brain regions. Genetic studies focused on PCA subjects are needed to uncover its underlying pathophysiology.

Design/Methods We assessed a cohort of 99 subjects with clinical and/or neuropathologic diagnosis of PCA collected at Mayo Clinic Florida in Jacksonville vs. 1,697 cognitively normal elderly controls collected at Mayo Clinic Florida in Jacksonville and Mayo Clinic Minnesota in Rochester. We genotyped the top LOAD risk SNPs from the nine LOAD GWAS loci and investigated associations with risk of PCA, adjusting for sex and APOE ?4 dosage in a multivariable logistic regression analysis paradigm.

Results The APOE ?4-tagging SNP, rs429358 significantly associated with risk of PCA (OR=3.40, p=6.1E-07). The ABCA7 rs3764650 SNP had nominally significant association with risk of PCA, consistent with its effect on AD risk (OR=2.19, p=0.011). No other associations were significant at p<0.05.

Conclusions These preliminary results in a small PCA cohort suggest that some genetic risk factors for this syndrome may overlap with those for AD, which is expected given their common neuropathology despite distinct regional distributions. Follow-up studies in larger cohorts are required to comprehend the underlying genetics of this atypical variant of AD.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
Minerva Carrasquillo (Mayo Clinic Florida)	The institution of Minerva Carrasquillo has received research support from NIA. The institution of Minerva Carrasquillo has received research support from Carl Angus DeSantis Foundation. The institution of Minerva Carrasquillo has received research support from Florida Department of Health. Minerva Carrasquillo has received personal compensation in the range of $500-$4,999 for serving as a Reviewer for Study Section with NIH.
	No disclosure on file
Melissa Murray, PhD (Mayo Clinic)	Dr. Murray has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Avid Radiopharmaceuticals. The institution of Dr. Murray has received research support from National Institute on Aging. The institution of Dr. Murray has received research support from Alzheimer's Association. The institution of Dr. Murray has received research support from Chan Zuckerberg Initiative.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Dennis W. Dickson, MD (Mayo Clinic)	Dr. Dickson has nothing to disclose.
Steven G. Younkin, MD, PhD (Mayo Clinic Jacksonville)	No disclosure on file
Bradley F. Boeve, MD, FAAN (Mayo Clinic)	Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from EIP Pharma. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care.
Neill R. Graff-Radford, MD, FAAN (Mayo Clinic Jacksonville)	The institution of Dr. Graff-Radford has received research support from Biogen. The institution of Dr. Graff-Radford has received research support from Lilly. The institution of Dr. Graff-Radford has received research support from Eisai. The institution of Dr. Graff-Radford has received research support from Biogen. Dr. Graff-Radford has received publishing royalties from a publication relating to health care.
Nilufer Taner, MD, PhD, FAAN (Mayo Clinic)	The institution of Dr. Taner has received research support from NIH.

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